The pathogenic role of stem cell-like memory T cells in rheumatoid arthritis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE141836 | GEO | 2021/12/01
REPOSITORIES: GEO
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Project description:Malondialdehyde-modified epitopes (MDA-epitopes) can elicit specific autoantibody that expressed oxidative stress arising in rheumatoid arthritis (RA). The purpose of this study was to discover and validate MDA-peptide adducts as novel biomarkers using concanavalin A affinity chromatography, 1D SDS-PAGE, in-gel digestion, and label-free nano-LC-MS, and evaluate levels of serum MDA, MDA-protein adducts, proteins and autoantibody isotypes against an unmodified and MDA-peptide from Taiwanese female patients with RA and healthy controls (HCs). Levels of serum MDA and MDA-protein adducts were significantly higher in RA patients versus HCs. Four differentially expressed novel MDA-peptides were selected that relative modification ratio were 2-fold differences to examine protein levels and assess autoantibodies to MDA-peptides in RA patients compared with HCs. Four of peptides are autoantigens. Furthermore, 4 MDA-peptides can induce more autoantibody isotypes that are statistical significance in RA patients compared to HCs. Serum IgG and IgM against MDA-peptides showed excellent diagnostic performance in discriminating among RA patients and HCs: area under the curve (AUC, 0.96 ~ 0.98), sensitivity (88.9% ~ 97.8%) and specificity (88.9% ~ 100%). Autoantibodies to MDA-epitopes indicate oxidative modifications occurring in RA, and might be useful as clinical markers fro RA diagnosis if further investigated.
2021-02-25 | PXD004546 | Pride
Project description:The development of T cells has been characterized as taking place over three stages: naïve (Tn), central memory (Tcm), and effector memory (Tem) cells. Recently, stem cell memory T cells (Tscm) were found to be the least-developed memory subset. We performed detailed analysis of the gene expression of human CD4+ T cells from patients with rheumatoid arthritis with clear distinction of the Tn, Tscm, Tcm, and Tem stages.
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Project description:Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Using regression correlation
2005-12-14 | E-GEOD-3824 | biostudies-arrayexpress
Project description:Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Keywords: all_pairs
2005-12-15 | GSE3824 | GEO
Project description:Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients as well as 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, including α/β-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways.
2022-02-23 | MTBLS4206 | MetaboLights
Project description:Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors. Keywords: disease state analysis
2004-11-04 | GSE1919 | GEO
Project description:Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria.
2005-10-11 | E-SMDB-1874 | biostudies-arrayexpress
Project description:We study a new pathogenic, glycolytic PD1+ B cell population in sites of inflammation of patients with Rheumatoid Arthritis (RA).
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Project description:The development of T cells has been characterized as taking place over three stages: naïve (Tn), central memory (Tcm), and effector memory (Tem) cells. Recently, stem cell memory T cells (Tscm) were found to be the least-developed memory subset. We performed detailed analysis of the gene expression of human CD4+ T cells with clear distinction of the Tn, Tscm, Tcm, and Tem stages. We sorted Tn, Tscm, Tcm, and Tem CD4+ T cells from the peripheral blood of six healthy volunteers to see the differences of gene expression between each developmental stage.
2015-05-12 | E-GEOD-61697 | biostudies-arrayexpress
Project description:Differences in DNA methylation have been reported in B and T lymphocyte populations, including CD4+ T cells, isolated from rheumatoid arthritis (RA) patients when compared to healthy controls. CD4+ T cells are a heterogeneous cell type with subpopulations displaying distinct DNA methylation patterns. In this study, we investigated DNA methylation using reduced representation bisulfite sequencing in two CD4+ T cell populations (CD4+ memory and naïve cells) in three groups: newly diagnosed, disease modifying antirheumatic drugs (DMARD) naïve RA patients (N=11), methotrexate (MTX) treated RA patients (N=18), and healthy controls (N=9) matched for age, gender and smoking status. Analyses of these data revealed significantly more differentially methylated positions (DMPs) in CD4+ memory than in CD4+ naïve T cells (904 vs 19 DMPs) in RA patients compared to controls. The majority of DMPs (72%) identified in newly diagnosed and DMARD naïve RA patients with active disease showed increased DNA methylation (39 DMPs), whereas most DMPs (80%) identified in the MTX treated RA patients in remission displayed decreased DNA methylation (694 DMPs). Interestingly, we also found that about one third of the 101 known RA risk loci overlapped (+/- 500 kb) with the DMPs. Notably, introns of the UBASH3A gene harbour both the lead RA risk SNP and two DMPs in CD4+ memory T cells. Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment.
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